Ovarian cancer is a major health problem and the most lethal gynecological malignancy. While more than 80% of patients survive the disease when it is diagnosed early, more than 75% of patients die within 5 years if the disease is diagnosed at a late stage. Thus, it is crucial that ovarian cancer is diagnosed and treated as early as possible. Since the disease is relatively rare, the biochemical testing must be characterized by extraordinary specificity and sensitivity. Unfortunately, the well-established ovarian cancer biomarker, CA125, does not meet these criteria. Under a screening scenario, the positive predictive value of CA125 is unacceptable and well-below 10%. There is a need to identify novel ovarian cancer biomarkers which, either alone or in combination, can bring about the desired sensitivity and specificity. We have shown in the past that many members of the human kallikrein family are promising new biomarkers for ovarian carcinoma. More specifically, the kallikreins hK5, hK6, hK7, hK8, hK10, hK11 and hK14 have been shown in preliminary clinical studies to have value in diagnosis and prognosis and some of them can complement CA125. In this application, we will examine in detail, and with a large series of samples, the diagnostic sensitivity and specificity of a panel of ovarian cancer biomarkers consisting of CA125, the 7 aforementioned kallikreins and six other promising molecules. In this effort, we have secured the participation of clinicians who have collected a large series of well-characterized serum samples from ovarian cancer patients [early and late stage] as well as patients with benign gynecological diseases and normal controls. In collaboration, we will analyze these samples by using immunofluorometric procedures developed in the applicant's laboratory. Statistical analysis will allow us to a) develop the most appropriate multiparametric models and b) establish the diagnostic sensitivity and specificity of the composite test. We hope that this novel combination will bring about a diagnostic sensitivity and specificity that is suitable for screening and for early diagnosis of asymptomatic patients. As noted, our application focuses on early detection. Relevance of this research to public health: By achieving early ovarian cancer diagnosis, it will be possible to reduce the burden of the disease by administration of effective treatment as early as possible. [unreadable] [unreadable] [unreadable]